The loss of voluntary control of sphincter muscles underlies urinary and anal incontinence. Urinary incontinence, the inability to voluntarily retain one's urine in one's bladder, is common among the elderly. Contraction of the detrusor muscle of the bladder may be voluntary, brought about stress, reflex or urge. Contraction of the detrusor muscle brought about by a stress results in involuntary urination unless the bladder sphincter muscle is voluntarily contracted. In the event that one has lost control of the bladder sphincter muscle, urination may be brought about by slight stress such as slight abdominal contractions during daily activities, sneezing, coughing, laughing, gas retention, surprises and countless other stimuli which may lead to contraction of the detrusor muscle. A similar principle underlies anal incontinence wherein one has diminished control of the anal sphincter muscle. Urinary and anal incontinence may be brought upon by ageing, trauma (such as in paraplegics), or congenitally related.
Vesicouretal reflux is the result of decreased ureteral resistance wherein urine from the bladder refluxes back into the kidney. This can result in the transport of bacteria from the bladder back up through the ureter, clayceal dilation, the renal pyramids and the kidneys and may lead to infections and recurrent pyelonephritis as well as cause physiological injury to the renal parenchyma. This may lead to renal failure.
Urinary incontinence, anal incontinence and vesicouretal reflux may be treated by increasing the resistance of passage through the urethra, the colon or rectum (or canalis analis), and the ureter, respectively, known as bulking processes
Attempts to treat urinary incontinence have involved hydraulic apparatuses, such as in WO 01/50833 and U.S. Pat. No. 4,969,474 and other controllable apparatuses such as prosthetic sphincters with inflatable cuffs as in U.S. Pat. No. 4,571,749 and WO 01/47433. Weight loss, exercise, medication and surgical operation usually involving the elevation of the bladder neck or constructing a increasing resistance through the urethra using the surrounding tissue or using a prosthetic material. Materials such as collagen, PTFE, silicone, and Teflon have been used to this end (references to be added).
Anal incontinence has also been addressed via controllable and operated devices such as in WO 01/47431. Vesicouretal reflux has been dealt with surgically (to extend the ureter, usually in the infant) and with antibiotics.
A principle object of the present invention is to provide a polyacrylamide hydrogel to increase the resistance in the relevant conduits in the treatment of incontinence and vesicouretal reflux.
U.S. Pat. No. 6,129,761 discloses the use of injectable hydrogel and cellular compositions towards this end. The compositions are cell suspensions comprising cells mixed with a biocompatible and biodegradable polymer. The polymer provides a medium and template for cell growth and cellular engraftment to the surrounding tissue. Cell growth coincides with polymer degradation to result in the desired tissue growth. The polymeric materials disclosed by U.S. Pat. No. 6,129,761 consist of alginates such as modified alginates, bacterial polysaccharides such as gellan gum, plant polysaccharides such as carrageenans, hyaluronic acids, polyethylene oxide-polypropylene glycol block copolymers, proteins such as fibrin, collagen, and gelatin, mixtures of polyethylene oxide and polyacrylic acid, cross-linked chitosan, photochemically cross-linked ethylenically unsaturated groups, macromers such as PEG-oligolactyl-acrylates, polyethylenimine, poly-lysine, poly(vinylamine), and poly(allylamine). U.S. Pat. No. 6,129,761 does not disclose the use of stable polyacrylamide hydrogels but rather degradable poly(vinylamine). Given the requirement of the polymer of the invention of U.S. Pat. No. 6,129,761 to degenerate according to the method of the invention, biostable polymers, such as the biostable polyacrylamide of the present invention is not suitable for the method of U.S. Pat. No. 6,129,761.
RU2148957 relates to a method for treating cases of vesicoureteral reflux using polyacrylamide hydrogel.
The substances for injection used thus far used are synthetic substances (teflon, silicone, coal particles) and natural substances (connective tissue extract, fat). The long-term effect has been relatively poor with relapses of incontinence among approximately half the treatments after one year of observation. Thus, there is a need to find a substance which is biocompatible with tissue but at the same time is not absorbed or excreted by the body (biostable). Moreover, the substance must have adequate rheological properties to act effectively.
An object of the present invention is to provide a biocompatible and bio-stable polyacrylamide hydrogel for increasing the resistance of conduits for the treatment of incontinence and vesicouretal reflux.